Transitive homology-guided structural studies lead to discovery of Cro proteins with 40% sequence identity but different folds.

ABSTRACT: Proteins that share common ancestry may differ in structure and function because of divergent evolution of their amino acid sequences. For a typical diverse protein superfamily, the properties of a few scattered members are known from experiment. A satisfying picture of functional and structural evolution in relation to sequence changes, however, may require characterization of a larger, well chosen subset. Here, we employ a "stepping-stone" method, based on transitive homology, to target sequences intermediate between two related proteins with known divergent properties. We apply the approach to the question of how new protein folds can evolve from preexisting folds and, in particular, to an evolutionary change in secondary structure and oligomeric state in the Cro family of bacteriophage

SUBMITTER: Roessler CG 

PROVIDER: S-EPMC2268138 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature